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The complex interaction of ATP and UTP with isolated hepatocytes. How many receptors?

S Keppens1

  • 1Department of Biochemistry, Faculty of Medicine, Katholieke Universiteit te Leuven, Belgium.

General Pharmacology
|March 1, 1993
PubMed

Insights

Adenosine triphosphate (ATP) triggers multiple effects in liver cells, including glycogenolysis and anti-glucagon activity, suggesting distinct ATP receptors. Uridine triphosphate (UTP) acts similarly to ATP, indicating shared receptor interactions.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Adenosine triphosphate (ATP) is a key signaling molecule with diverse physiological roles.
  • Hepatocytes, or liver cells, are central to metabolic regulation, including glucose homeostasis.
  • Understanding receptor-mediated signaling in hepatocytes is crucial for metabolic research.

Purpose of the Study:

  • To investigate the distinct receptor-mediated effects of ATP on isolated hepatocytes.
  • To differentiate the signaling pathways activated by ATP and its analogues.
  • To identify potential novel receptors involved in ATP signaling in liver cells.

Main Methods:

  • Isolated hepatocyte studies.
  • Measurement of intracellular calcium levels.
  • Pertussis toxin treatment to assess G-protein involvement.
  • Assessment of glycogenolysis and enzyme activity (glycogen phosphorylase, glycogen synthase).
  • Use of ATP analogues (2MeSATP, ADP beta S) and UTP.

Main Results:

  • ATP induced glycogenolysis via IP3/calcium and activated phospholipase D, independent of cAMP.
  • Pertussis toxin selectively blocked ATP's anti-glucagon effect, not its glycogenolytic effect.
  • ATP analogues (2MeSATP, ADP beta S) showed differential effects, with reduced IP3 generation and phorbol ester-sensitive glycogenolysis.
  • UTP mimicked ATP's effects, suggesting interaction with the same receptor(s).

Conclusions:

  • Hepatocytes possess multiple ATP receptors mediating distinct signaling pathways.
  • At least three receptor types are proposed: one activating phospholipase C, another activating phospholipase D, and a third inhibiting adenylate cyclase.
  • These findings provide insights into the complex purinergic signaling network in liver cells.

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